(E)-3-(1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)-N-(4-methoxybenzyloxy)acrylamide | 1370748-91-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: (E)-3-(1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)-N-(4-methoxybenzyloxy)acrylamide
• 英文别名: (E)-3-[1-(1H-benzimidazol-2-ylmethyl)triazol-4-yl]-N-[(4-methoxyphenyl)methoxy]prop-2-enamide
• CAS: 1370748-91-6
• 化学式: C₂₁H₂₀N₆O₃
• 分子量: 404.428
• InChiKey: MCCXWCVPAIHUEY-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)-N-(4-methoxybenzyloxy)acrylamide 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到(E)-3-(1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide
  参考文献：
  名称：

  Discovery and Extensive in Vitro Evaluations of NK-HDAC-1: A Chiral Histone Deacetylase Inhibitor as a Promising Lead

  摘要：

  Herein, further SAR studies of lead compound NSC746457 (Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X. W.; Chen, M.; Fang, L. Y.; Sun; D. X.; Wang. P. G. J. Med. Chem. 2008, SI, 7417-7427) were performed, including the replacement of the trans-styryl moiety with a 2-substituted benzo-hetero aromatic ring and the introduction of a substituent onto the central methylene carbon. A promising chiral lead, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide (12, NK-HDAC-1), was discovered and showed about 1 order of magnitude more potency than SAHA in both enzymatic and cellular assays. For the in vitro safety tests, NK-HDAC-1 was far less toxic to nontransformed cells than tumor cells and showed no significant inhibition activity against CYP-3A4. The pharmaceutical properties (LogD, solubility, liver micrsomal stability (t1/2), plasma stability (t1/2), and apparent permeability) strongly suggested that NK-HDAC-1 might be superior to SAHA in bioavailability and in vivo half-life.

  DOI：

  10.1021/jm201496g
• 作为产物：
  描述：

  2-氯甲基苯并咪唑 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 叔丁醇 为溶剂， 生成 (E)-3-(1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)-N-(4-methoxybenzyloxy)acrylamide
  参考文献：
  名称：

  Discovery and Extensive in Vitro Evaluations of NK-HDAC-1: A Chiral Histone Deacetylase Inhibitor as a Promising Lead

  摘要：

  Herein, further SAR studies of lead compound NSC746457 (Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X. W.; Chen, M.; Fang, L. Y.; Sun; D. X.; Wang. P. G. J. Med. Chem. 2008, SI, 7417-7427) were performed, including the replacement of the trans-styryl moiety with a 2-substituted benzo-hetero aromatic ring and the introduction of a substituent onto the central methylene carbon. A promising chiral lead, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide (12, NK-HDAC-1), was discovered and showed about 1 order of magnitude more potency than SAHA in both enzymatic and cellular assays. For the in vitro safety tests, NK-HDAC-1 was far less toxic to nontransformed cells than tumor cells and showed no significant inhibition activity against CYP-3A4. The pharmaceutical properties (LogD, solubility, liver micrsomal stability (t1/2), plasma stability (t1/2), and apparent permeability) strongly suggested that NK-HDAC-1 might be superior to SAHA in bioavailability and in vivo half-life.

  DOI：

  10.1021/jm201496g

文献信息

• Discovery and Extensive <i>in Vitro</i> Evaluations of NK-HDAC-1: A Chiral Histone Deacetylase Inhibitor as a Promising Lead
  作者：Jingli Hou、Zhonghua Li、Qinghong Fang、Congran Feng、Hanwen Zhang、Weikang Guo、Huihui Wang、Guoxian Gu、Yinping Tian、Pi Liu、Ruihua Liu、Jianping Lin、Yi-kang Shi、Zheng Yin、Jie Shen、Peng George Wang

  DOI：10.1021/jm201496g

  日期：2012.4.12

  Herein, further SAR studies of lead compound NSC746457 (Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X. W.; Chen, M.; Fang, L. Y.; Sun; D. X.; Wang. P. G. J. Med. Chem. 2008, SI, 7417-7427) were performed, including the replacement of the trans-styryl moiety with a 2-substituted benzo-hetero aromatic ring and the introduction of a substituent onto the central methylene carbon. A promising chiral lead, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide (12, NK-HDAC-1), was discovered and showed about 1 order of magnitude more potency than SAHA in both enzymatic and cellular assays. For the in vitro safety tests, NK-HDAC-1 was far less toxic to nontransformed cells than tumor cells and showed no significant inhibition activity against CYP-3A4. The pharmaceutical properties (LogD, solubility, liver micrsomal stability (t1/2), plasma stability (t1/2), and apparent permeability) strongly suggested that NK-HDAC-1 might be superior to SAHA in bioavailability and in vivo half-life.